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首页> 外文期刊>Clinical and diagnostic laboratory immunology >The Tumor Necrosis Factor-Inducing Potency of Lipopolysaccharide and Uronic Acid Polymers Is Increased when They Are Covalently Linked to Particles
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The Tumor Necrosis Factor-Inducing Potency of Lipopolysaccharide and Uronic Acid Polymers Is Increased when They Are Covalently Linked to Particles

机译：当脂多糖和糖醛酸聚合物与颗粒共价连接时，其诱导肿瘤坏死因子的能力增加。

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Lipopolysaccharide (LPS) and polymers of the uronic acid family stimulate monocytes to produce tumor necrosis factor (TNF). The TNF-inducing potency of these polysaccharides may depend on their supramolecular configuration. In this study detoxified LPS and uronic acid polymers have been covalently linked to particles which have been added to monocytes under serum-free conditions. Reducing the size of mannuronan from 350,000 to 5,500 Da (M-blocks) led to a 10- to 100-fold reduction in TNF-inducing potency. However, covalently linking the M-blocks to monodisperse suspensions of magnetic particles increased the TNF-inducing potency by up to 60,000-fold. Also, the TNF-inducing potency of glucuronic acid polymers was increased when they were linked to particles, but no potentiation was observed with guluronic acid blocks covalently attached to particles. Furthermore, O chains of LPS (detoxified LPS) became potent TNF inducers when they were presented to monocytes on a particle surface. No activation of the LPS-responsive SW480 adenocarcinoma cells was found with detoxified LPS or M-block particles, suggesting a preference for cells expressing CD14 and/or other membrane molecules. The potentiating effects were not restricted to polymers attached to aminated magnetic particles. Of particular interest, we found that short blocks of mannuronan induced TNF production also when covalently linked to biodegradable, bovine serum albumin particles.
机译：脂多糖（LPS）和糖醛酸家族的聚合物刺激单核细胞产生肿瘤坏死因子（TNF）。这些多糖的TNF诱导能力可能取决于其超分子构型。在这项研究中，已将解毒的LPS和糖醛酸聚合物与无血清条件下添加到单核细胞的颗粒共价连接。将甘露糖醛聚糖的大小从350,000 Da减少到5,500 Da（M嵌段）导致TNF诱导能力降低10到100倍。但是，将M嵌段共价连接到磁性颗粒的单分散悬浮液上，可将TNF诱导能力提高多达60,000倍。同样，当葡糖醛酸聚合物与颗粒连接时，其诱导TNF的能力增加，但是对于共价连接到颗粒上的古洛糖酸嵌段，没有观察到增强作用。此外，LPS的O链（解毒的LPS）在呈递至颗粒表面的单核细胞时成为有效的TNF诱导剂。用解毒的LPS或M-block颗粒未发现LPS反应性SW480腺癌细胞的激活，表明对表达CD14和/或其他膜分子的细胞的偏爱。增强作用不限于附着在胺化磁性颗粒上的聚合物。特别令人感兴趣的是，我们发现，当与生物可降解的牛血清白蛋白颗粒共价连接时，短链甘露糖醛聚糖也诱导TNF的产生。

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